Dibenzoylethylene compounds and method for producing the same



Patented June 9, 1953 uNiTEo STATES DIBENZOYLETHYLENE COMBGUNDS'; METHOD, FOR. PRODUCING THE SAME;

Moses Wolf ('ffoldlierg,- UpperMontclai'r; and Al bert I'sraelRaclilin, Maywood; N J1, assignors to Hoffmann-La; Roche Inc, Nutley, N; J a cor poration: of New Jersey i I No Drawing. Application Neatbeg 24 ,11si50,

Serial- No. 137,491.

8 Claims. (Cl. 2'69 30 9-'.6).

The present invention relates todibenzoy-lethylene-compounds and more particularly to l-benzoyl-2-[p-(4,5-dihydro 2 imidazolyllbenzoyll ethylene, 1-benzoyl 2 ('p-quanylbenzoyl) ethylene, the acid addition salts of the aforesaid compounds and the method of producing the same. The new compounds are useful as antitrichomonas compounds.

' The l-benzoyl -2 [p (.4,5-dihydro-2-imldazolyDbenzoyl] ethylene can be represented" by the following formula:

.' NP CH2. and the 1"-benzoy1'-2-(p-guanylbenzoyl)ethylene canberepresented by the following formula;

suspension of l-benzoyl-Z-(p-cyanobenzoyl)ethylene in a lower alcohol, such as methanol or ethanol, with an equivalent amount of hydrogen chloride or a small excess thereof. The l-benzoyl-2-(p-cyanobenzoyl) ethylene can, in turn, be prepared by reacting acetophenone with p-cyanophenylglyoxal, which is prepared by oxidizing p-cyanoacetophenone with selenium oxide.

The following examples will serve to illustrate the preparation of the new intermediates.

EXAMPLE A p-Cyanophenylglyoacal To a mixture of 500 cc. of dioxane and 20 cc. of water were added 56 grams of finely divided selenium dioxide. The mixture was stirred at 50 C. until the selenium dioxide had dissolved, and then 72.5 grams of p-cyanoacetophenone were added. The mixture was refluxed with stirring for 6 hours, during which time black metallic selenium precipitated; --Stirring was continued without heating for 18 hours, and then the seleniumwas removed byfiltration. The solvent was removed invac'u'o-and the hot' residue was dissolved 'in 30 0' cc. of acetone. The acetone was flashed off and the residue was distilled on an oil bath. The p-cyanophenylglyoxal wasobtained: as a heavy, viscous oil boiling at: 104410 C:/-1'.5='mm. 1A sampleofthe oily material was converted to thehydrate by trituration with water! Afterseveral crystallizationsfrom nitromethane, the white crystalline p-cyanophenyl glyoxal hydrate meltedatQG-lOO C.

EXAMPLE-B 1 -b ena oyl-2 (p -cyanobehzby l) ethylene v A mixture, of 19.4 gramsofp-cyanophenylg-l-yoxah. 60. grams of acetophenone and- 565 cc. of. acetic anhydride .was heated for 2.5 hours in an-oil bath-at-145-l50" Vacuum was applied to the, hot; mixtureto. remover themacetic acid formed, andafter stand-ingforv 24 hours. at room temperature, the; mixture was triturated with. 30 cc., of absolute ethanol, filtered,,-and. washed twice with 30,- cc.. ot absolute ethanol, and then 30 cc. of ether. The yellow product thus obtained was recrystallized from 2300 cc. of methanol, yielding yellow crystals of l-benzoyl-Z-(pcyanobenzoyDethylene, M. P. 143-145 C.

EXAMPLE C l-benzoyl-Z- [p- (a-imz'nomethoxymethyl) benzoyl] ethylene hydrochloride A stirred suspension of 9 grams of l-benzoyl- 2-(p-cyanobenzoyl) ethylene in cc. of methanol was cooled in an ice bath for 20 minutes Dry hydrogen chloride was passed into the suspension for 6 minutes. Complete solution resulted 2 minutes after starting the addition of the hydrogen chloride. The solution was allowed to stand at room temperature for 72 hours. Orange-colored crystals began to separate after 2.5 hours of standing at room temperature. After the expiration of '72 hours, the orange-colored crystals were filtered, washed with ether, and dried in vacuo over solid potassium hydroxide. The product was recrystallized several times from ethanol to yield 1-benzoyl-2-[p-(a-iminomethoxymethyD-benzoyll ethylene hydrochloride, M. P. 253- 255 C.

The following examples will serve to illustrate the preparation of the guanyl and imidazolyl substituted compounds.

3 EXAMPLEI anhydrous ethylenediamine was refluxed for.-6

hours. The solution was filtered from a small amount of insoluble matter and the filtrate was cooled to 4 C. The crystallineproduct which formed was filtered oil and had a M. P. of 276- 279 C. with decomposition. The mother liquor was concentrated to '7 cc. and cooled at 4 C. A second crop of the product having the melting water, yielding 1-benzoy1-2-(p-guanylbenzoyl)- ethylene hydrochloride as orange-colored crystals, M. P. 252-253 C. A sample of this compound recrystallized from acetonitrile water melted at 253-255 C.

The free base, 1 -benzoyl-2-(p-guanylbenzoyl) ethylene, can be liberated from a solution of the hydrochloride by the addition of 0.1 N sodium hydroxide.

We claim: 1. A compound selected from the group con- I sisting of a 1 benzoyl 2 [p (4,5 dihydro 2- point 269-279" C. with decomposition was obtained. The combined fractions were recrystallized from a mixture of 120 cc. of acetonitrile, one cc. of concentrated hydrochloric acid and 18 cc. of water, giving a product melting at 278-279 C. with decomposition. When this product was recrystallized from alcohol, pure l-benzoyl-Z-[p- (4,5-dihydro-2-imidazolyl) benzoyl] ethylene hydrochloride was obtained in the form of orangecolored cubes, M. P. 277279? C. These crystals tend to retain alcohol oi crystallization.

The free base, l-benzoyl-Z-[p-4,5-dihydro-2- imidazolyDbenzoyllethylene, was obtained from a solution of the hydrochloride by the addition of 0.1 N sodium hydroxide. Recrystallized from ethanol, the free base was obtained in the form of yellow crystals, M. P. 181-183? C.

EXAMPLE 2 1 -benz0yZ-2- (p-guanylbenzoyl) ethylene hydrochloride 3.5 grams of l-benzoyl-2-[p-(a-iminomethoxymethyl) benzoyllethylene hydrochloride and 50 cc. of methanolic ammonia (11 per cent) were heated at 70 C. in a pressure bottle for 6 hours. After cooling to room temperature, a small amount of insoluble matter was removed by filtration, and the mother liquor was evaporated to dryness in vacuo. The residue was recrystallized from a mixture of 180 cc. of acetonitrile, 3 cc. of concentrated hydrochloric acid. and 22 cc. of

imidazolyl) benzoyl] ethylene and l-benzoyl-2- (pguanylbenzoyD-ethylene, and the acid addition salts thereof.

2. 1 benzoyl 2 (p guanylbenzoyl) ethylene Y hydrochloride.

3. 1 benzoyl 2 (p guanylbenzoyDethylene.

4. 1 benzoyl 2 [p (4,5 dihydro 2- imidazolyl) benzoyl] ethylene hydrochloride.

- 5. l-benz0yl-2-Ep-(4,5 dihydro-Z-imidazolyhbenzoyl] ethylene.

6. The process which comprises reacting a cooled suspension of 1 benzoyl 2 (p cyanobenzoyl) ethylene in a lower alcohol with approximately an equivalent amount of hydrogen chloride so as to produce a 1-benzoyl-2-[p-(aiminoalkoxymethyl) benzoyl] ethylene hydrochloride, and reacting the latter compound with a member of a group consisting of ammonia and ethylenediamine.

7. The process which comprises reacting 1- ben'zoyl 2 [p (a. iminometho-xymethyD- benzoyllethylene hydrochloride with ammonia so as to form 1-benzoyl-2-(p-guanylbenzoyl)- ethylene hydrochloride.

8. The process which comprises reacting lbenzoyl 2 [p (a. iminomethoxymethyD- benzoyllethylene hydrochloride with ethylenediamine to form l-benzoyl-Z-[p-(4,5-dihydro-2- imidazolyl) benzoyl] ethylene hydrochloride.

' MOSES WOLF GOLDBERG. ALBERT ISRAEL RACHLIN;

No references cited. 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 1-BENZOYL - 2- (P- (4,5-DIHYDRO - 2 IMIDAZOLYL) BENZOYL) ETHYLENE AND 1-BENZOYL-2-(PGUANYLBENZYL)-ETHYLENE, AND THE ACID ADDITION SALTS THEREOF. 